Advancing Age and Risk From the Elevated Atherogenic Index: Triglyceride (TG) to High‐Density Cholesterol (HDL‐C) Ratio

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD), but this association diminishes with age. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio, also known as the atherogenic index, is a surrogate marker for small-density low-density lipoprotein cholesterol (sdLDL-C), a more specific LDL-C biomarker associated with ASCVD. It is unclear if age influences the association between the atherogenic index and incident ASCVD. We aimed to assess the influence of advancing age and an elevated atherogenic index on the risk of ASCVD. METHODS: We included UK Biobank participants without self-reported, pre-existing ASCVD and with available lipid biomarkers. We then estimated the effect of age on the associations between TG: HDL-C quintiles and incident ASCVD using a nonlinear Cox regression model. RESULTS: Data from 342,979 participants were analyzed. The mean age was 56 ± 8 years (55% females), and the mean duration of follow-up was 12.7 ± 2.8 years. Individuals who developed clinical ASCVD were older (mean age at baseline 60 vs. 56 years, p < 0.001) and had a higher mean TG to HDL-C ratio (3.72 vs. 3.03, p < 0.001). Higher quintiles of the TG/HDL-C ratio (Q2-Q5) were associated with an increased risk of ASCVD compared to the first quintile (Q1) across all age groups up to 65 years. However, there was a declining risk with advancing age, as indicated by the HR for Q5 versus Q1 at ages 45, 55, and 65, which were 1.60, 1.37, and 1.07, respectively. CONCLUSION: The association between the TG/HDL-C ratio (atherogenic index) and incident ASCVD steadily attenuates with age. In adults over 65, an elevated ratio may be associated with a lower risk of incident ASCVD. These findings may reflect changes in metabolic atherosclerotic risk or a survival effect associated with aging and require further investigation.